1. Field of the Invention
The field of this invention relates to inhalation therapy devices and incentive spirometry. More particularly, the field of the present invention relates to an apparatus and display method for interactive training in the use of metered dose aerosol inhalers.
2. The Background Art
Devices for dispensing aerosol pharmaceuticals have become the favored medication delivery system in the treatment of many respiratory diseases. The use of inhaled sympathomimetic bronchodilators has been widespread since the 1960s. Moreover, the past several years have witnessed a rapid increase in the prescription of inhaled corticosteriods. In addition to these medications, whose primary site of action is in the respiratory tract and lungs, the inhaled route is being explored for the delivery of systemically acting pharmaceuticals.
Inhaled pharmaceuticals have taken a central role in the treatment of common diseases such as asthma, bronchitis, and emphysema, and their use is expected to increase. Approximately 10 to 15 million people in the United States suffer from asthma, and its prevalence in the general population is increasing. Childhood asthma is the single greatest cause of missed school days in the United States, accounting for an estimated 10 million absences in 1990. Chronic obstructive lung disease (COPD) of all types is estimated to affect as many as 30 million in the U.S. See Petty, "Chronic Obstructive Pulmonary Disease - Can We Do Better?," Chest, 97:2(S), (1990).
Inhaled aerosol treatment has been found to be extremely effective for respiratory disease, since medication is delivered directly to the site of action. In comparison with other routes of administration, this reduces the dosage required and in some instances speeds the onset of action. Inhalation of a pharmaceutical resembles parenteral injection because it bypasses the liver and thus reduces hepatic metabolic degradation of the active compound. See Reed, "Aerosol Glucocorticoid Treatment of Asthma," American Review of Respiratory Disease, 141:S82-S88, (1990).
it has been found that aerosol delivery of a pharmaceutical such as a glucocorticoid has significant advantages over oral administration in terms of reducing adverse side effects. For example, osteoporosis, compression fractures of the vertebrae, and aseptic necrosis of the femoral head are well known serious complications of prolonged oral glucocorticoid treatment. These side effects have not been reported in patients who have received glucocorticoids through aerosol therapy. Id. Similarly, adverse reactions caused by bronchodilators, including tremor and tachycardia, are reduced when delivery is switched from oral to inhaled routes.
Such benefits are due at least partially to the reduced dosage necessary to effect therapeutic benefit when these pharmaceuticals are administered through inhalation. When aerosol glucocorticoids are substituted for oral treatment, the dose of prednisone or prednisolone required to maintain control of airways can be more effective than an administration of 20-80 times the dose of the same drug by mouth. Id.
As treatment of diseases with aerosol pharmaceuticals such as aerosol glucocorticoids increases, there is a need for more efficient delivery systems to ensure proper delivery of the therapeutic agent into the lungs. Proper inhalation techniques are essential in order that the inhaled pharmaceutical such as a glucocorticoid is delivered to the receptor sites in the lungs. If the glucocorticoid aerosol lands in the pharynx or other part of the respiratory tract other than the lungs, its beneficial effect is lost or reduced. Moreover, the improperly delivered aerosol glucocorticoid can be digested by the system, resulting in the adverse side effects which aerosol therapy is intended to overcome.
A major problem in the use of aerosol pharmaceuticals is achieving deposition of the aerosol at the target receptor sites within the airways and lungs. Pressurized metered dose inhalers have been designed to deliver a precise amount of medicine in the form of a cloud of aerosol droplets having an aerodynamic diameter which is optimal for reaching the conducting airways of the lungs. Similarly, dry powder generators have been designed to deliver a measured amount of dry particles, such as sodium cromoglycate, to the lungs.
The human lung divides dichotomously for some 23 generations until the alveoli are reached. Inhaled aerosol medication particles must move through airways of ever decreasing size, at decreasing flow rates, while constantly changing direction. As a result primarily of impaction on the sides of the inhaler device, the mouth, and the oropharynx, only a small fraction of the dose from a aerosol inhaler is actually deposited in the lungs. This is true even when the inhaler is used according to the manufacturer's instructions. When the patient uses the inhaler incorrectly, the dosage delivered is greatly reduced. Newman, et al., "Deposition of Pressurized Aerosols in the Human Respiratory Tract," Thorax, 36: 52-55 (1981). Patterson et al., "Patient Error in Use of Bronchodilator Metered Aerosols," British Medical Journal 10:76 (1976).
So many patients use inhalers improperly that poor inhalation technique is believed to be the main reason for the lack of efficacy of aerosol bronchodilators and aerosol glucocorticoids. Because breathing habits are subliminal and developed over the course of a lifetime, it is especially difficult for a patient to alter inhalation techniques in order to increase the efficacy of an aerosol medication. Reed, "Aerosol Glucocorticoid Treatment of Asthma," American Review of Respirator Disease, 141:S82-S88 (1990). (cite Lancet editorial)
The literature is replete with examples which indicate the magnitude of this problem. In 1976, Orehek, et al. tested 20 asthmatic patients using bronchodilator drugs. Of these, only five used proper inhalation techniques. See Orehek, et al. "Patient Error in Use of Bronchodilator Metered Aerosols," British Medical Journal, 10:76 (1976). It was also reported in 1980 that 47% of 30 patients hospitalized for asthma used an incorrect inhalation technique. Shim and Williams, The American Journal of Medicine 69:891-894 (1980).
Although coaching can improve the ability to use inhalers, it has been found that many patients revert to an incorrect inhalation technique within a short period. Importantly, it has been concluded that regular subsequent monitoring of inhalation techniques are necessary. Patterson, et al., "Use of Pressurized Aerosols by Asthmatic Patients," British Medical Journal, 10:76-77 (1976). Because the full potential of aerosol pharmaceuticals cannot be achieved unless patients understand how to properly use inhaler devices, there is a need to more effectively train patients to follow a proper sequence of inhalation steps to be followed in order to ensure maximum delivery of an aerosol pharmaceutical to receptor sites in the lungs.
Methods of teaching proper inhalation may require complex breathing patterns. Aerosol pharmaceuticals are deposited in the lungs by three principal mechanisms: inertial impaction, gravitational sedimentation, and diffusion. Other mechanisms of deposition such as electrostatic interactions with opposite charges in airways walls are so small as to be insignificant relative to these three processes.
Impaction of aerosol particles or droplets on the sides of the oropharynx and airways increases with increasing particle size and/or flow rate of inspiration. Sedimentation is a critical factor in determining the amount of aerosol deposited in the alveolar bed and conducting airways. Sedimentation is time dependent process and the level of aerosol deposition is therefore a function of the duration of the breath holding pause following inhalation.
The mechanisms of deposition have been clarified by scintigraphic studies. Such experiments demonstrate that inhalation at higher flow rates increases deposition in the oropharynx and upper airways, while decreasing deposition in the lower airways. These studies also illustrate an increased deposition with longer breath holding because the amount of aerosol remaining airborne decreases exponentially with time. In one study, radiolabelled aerosols were inhaled at varied lung volumes and flow rates and radiographic images taken to detect the distribution of aerosols within the respiratory tract of patients with obstructive airways disease. This study showed that increasing the length of breath holding from 4 to 10 seconds effectively doubled the percentage of medication deposited in the lungs. Newman, et al., "Effects of Various Inhalation Modes on the Deposition of Radioactive Pressurized Aerosols," European Journal of Respiration," Dis. Suppl. 119, 63:7 (1982).
Conventional methods and apparatus for inhalation training lack adequate visual representation of these and other processes that govern the actual delivery of the aerosol to the receptor sites in the lungs. Accordingly, there is a need for an inhalation training apparatus which will provide the patent and physician with a real time, interactive representation of the inhalation process. Ideally, this would provide visual feedback representing the actual distribution of inhaled aerosol in the lungs and show with reasonable accuracy the amount of aerosol delivered to the receptor sites. Such feedback would convey a conceptual understanding of the proper inhalation process, and thereby increase the likelihood that the patient would retain the correct technique.
Several attempts have been made to improve the usage of inhalers. For example, some devices attach the inhaler to spacer tubes which extend the channel through which the aerosol flows. A typical example of this device is U.S. Pat. No. 4,809,692 issued Mar. 7, 1989. This device provides an extended channel for the flow of aerosol in the form of a mask which fits over the nose and mouth of a child. The device includes an inhalation valve in which a sound is generated upon inhalation and exhalation.
Other attempts to improve the use of inhalers include providing large non-pressurized chambers or reservoirs for holding the aerosol prior to inhalation. These devices lessen or obviate the requirement for coordinating actuation of the inhaler with inspiration. Some of these devices also feature auditory signals which provide the user with feedback when the inhalation flow exceeds a desired rate. Examples of such devices are Sacker et al., U.S. Pat. No. 4,484,577, issued Nov. 27, 1984, Zoltan et al., U.S. Pat. No. 4,926,852, issued May 22, 1990, Zoltan, U.S. Pat. No. 4,790,305, issued Dec. 13, 1988, Grimes, U.S. Pat. No. 4,210,155, issued Jul. 1, 1980 and Sperry, U.S. Pat. No. 4,852,561, issued Aug. 1, 1989. While these devices have been found effective, many patients do not utilize them because of the inconvenience caused by their bulk and the patient's self consciousness about the use of such devices in public.
The foregoing devices still, however, provide an inadequate means for training the patient in proper inhalation techniques. While auditory signals may provide some feedback for breath intake, there is no means for measuring a patient's performance with a standard or optimum technique for delivering medication to the receptor sites in the lungs. There is also no means for showing whether the aerosol is in fact being delivered properly to the lungs. In addition, these devices provide no means for active guidance for breath holding at the end of aerosol inspiration.
Still other conventional inhaler devices attempt to maximize the delivery of an aerosol pharmaceutical to the receptor sites in the lungs by employing improved actuating mechanisms. An example of such a device is Wasf, U.S. Pat. No. 4,664,107, issued May 12, 1987. Similarly, Johnson et al., U.S. Pat. No. 4,803,978, issued Feb. 14, 1989 provides an inhaler device wherein the release of medication is actuated by a pressure drop at the time of inhalation. These devices are more complex and expensive than the simple inhaler devices currently in general use. Accordingly, their use has not become widespread. Moreover, while these devices address the problem of coordinating inhaler actuation with the start of inspiration, they do not address the need for teaching proper inhalation flow rate, volume, and breath holding time in order to maximize the amount of medication delivered to the receptor sites.
Typical inspiratory training devices also include a number of incentive spirometers such as Sharpless et al., U.S. Pat. No. 4,391,283, issued Jul. 5, 1983, or Lester, U.S. Pat. No. 4,284,083, issued Aug. 18, 1981. Conventional incentive spirometers include mechanical means for allowing the user to see a visual indication of the rate of inspiration or expiration. The user can then compare this with a desired value. The object of these devices is the promotion of post-operative recovery of the lungs. To effect this they provide an incentive for the patient to expand the lungs. These devices are not designed for teaching techniques for inhalation of aerosol medication.
Therefore, such conventional devices have little or no usefulness in training a patient to use an inhaler device properly. For example, the incentive in the '283 patent resides in observing a cylinder or sphere raised to a predetermined height in a tube. This has the disadvantage of merely measuring flow rate or volume of inhalation. Thus, it ignores many of the parameters responsible for specific deposition patterns of an aerosol pharmaceutical at the receptor sites in the bronchial tree. Here again, the patient is not provided with any visual feedback relating to the delivery of an aerosol medication to the lungs.
Elson, U.S. Pat. No. 4,241,739, is a typical incentive spirometer device intended to promote post-operative recovery. This device incorporates a flow meter, processing means and display means to provide visual feedback of the volume of airflow during inhalation. However, this device is of limited usefulness in that it only takes into account a few limited parameters in defining the program of respiratory exercise which the patient is to follow. The parameters include minimum flow rate to be achieved, minimum total volume to be inhaled, the time that the patient is to hold the inhaled volume, and the number of times the patient is to be required to inhale the predetermined minimum volume. The feedback to the patient consists of display windows comprising an array of light emitting diodes which display alpha-numeric characters. For example, the flow rate of the air inhaled by a patient is integrated to determine volume. If the volume of inspired air by the patient exceeds that amount which was set by the therapist into a volume register, the display panel is instructed to display the word "Good." This device has the disadvantage of limited feedback to the patient. Also, the feedback is not interactive. The values of the desired parameters such as minimum flow rate, minimum total volume to be inhaled or number of inhalations must be predetermined by the therapist and then programmed into various memory registers. The patient's responses are then compared against the predetermined values. Accordingly, this device, in principle, is not too far removed from a conventional mechanical incentive spirometer having feedback such as the distance an object rises in a calibrated tube.
A typical inhalation training device also includes a "Respiratory Biofeedback and Performance Evaluation System" Hillsman, U.S. Pat. No. 3,991,304 1976. This system relates to performance evaluation and training in repetitive breathing patterns. The object of this system was to improve the efficiency of a patient's ongoing breathing pattern, in order to increase oxygen supply and carbon dioxide elimination to and from the lungs. The uses contemplated for the Hillsman system did not achieve commercial success or widespread application. These uses include repetitive breathing patterns characterized in terms of three inter-related factors: rate of respiration, tidal volume, and inspiratory to expiratory time ratio. The system provides a conventional visual display for patient training wherein volume of air inspired or expired is plotted on a vertical axis against time as represented by the horizontal axis, with cycle time or breathing rate adjustable from 0 to 40 cycles per minute.
The conventional Hillsman training system focuses primarily on the cyclic breathing of individuals with obstructive or restrictive lung diseases, with or without the concurrent inhalation of aerosols. Training is also contemplated for individuals engaged in intermittent positive pressure breathing, the playing of musical instruments, scuba diving, and Lamaze-type obstetrical breathing exercises. Techniques associated with cyclic breathing are different in nature from those involved in a discrete, individual inhalation and breath hold maneuver. A conventional inhalation training system does not address the particular problems associated with the use of a hand held metered dose inhaler. For example, maximizing the delivery of medication from a metered dose inhaler involves a discrete, one-time action of a single inspiration and breath hold maneuver wherein no relation exists with breathing cycles immediately prior to or subsequent to the studied inhalation itself.
Another example of a conventional inhalation trainer is a device marketed by Vitalograph Corporation of the United Kingdom and Lenexa, Kans. This device includes a metered dose inhaler connected with a flow sensor and means for calculating flow and volume of air. The display of feedback to the user is in the form of lights of alternating color and an analog needle gauge which indicates flow rate, including a desired flow range. During the practice inhalation maneuver, the patient is told to keep the needle gauge within the desired flow range. At the completion of the maneuver the device displays three colored lights, labeled "firing," "delivery," and "breath hold". A green light indicates that the patient performed the corresponding aspect of the inhalation correctly. A secondary optional display provides an incentive device utilizing several lights overlain with cartoon figures painted on a plastic overlay. At the conclusion of the maneuver the lights are illuminated under certain of the cartoon figures, indicating thereby whether the three aforementioned aspects of the maneuver were performed correctly.
This device has the disadvantage that the feedback provided by the colored lights is not fully interactive. In addition, the device does not provide feedback regarding the patient's performance across the full time course of the maneuver, since the flow gauge represents only an instantaneous indication of flow. In addition, the device does not allow the operator to change the values which differentiate between correct and incorrect performance. Furthermore, the device does not provide a printed or electronically stored record of performance.
The prior art also includes an MDI Biofeedback Training and Evaluation System, Hillsman Patent 4,984,158 1991. As in the system described in Hillsman 1976, this training system is based upon a volume versus time graph of patient breathing patterns. The system employs an MDI canister, flow measurement means, processor, and means for displaying actual breathing and desired breathing patterns. One of the integral elements of the Hillsman system is the measurement of both inspiration and expiration prior to, during, and after use of a MDI. Another element is the identification of the patient's lung volume at the point of start of inhalation.
Scintigraphic studies of aerosol deposition have shown that lung volume at start of inhalation is of secondary importance as a determinant of the level of aerosol deposition, in comparison with the factors of inhalation rate and duration of breath holding. For example, Newman, et. al reported that varying the start of inhalation point between 20%, 50% and 80% of lung capacity resulted in little difference in the percentage of aerosol deposited in the lunge, provided that proper inhalation rate and breath hold time were observed. Newman, Stephen P., et. al., "Effects of Various Inhalation Modes on the Deposition of Radioactive Pressurized Aerosols", European Journal Respiratory Disease Supp. 119, Vol 63, 1982. Thus, it appears that the careful measurement of end expiration point as a means of enforcing start of inhalation from low lung volume is of limited value. The inventors have in fact found that insisting that inhalation begin from low lung volume can actually impair the patient's ability to perform an optimal maneuver. This is because inhaling to full vital capacity at the desired low flow rate takes additional time, and increases the discomfort felt during a full ten second breath hold period.
The improvements offered by the present invention relate to both the manner in which airflow into the lung is measured and the structure and content of information displayed to operator, patient and physician. In the present invention the measurement of expiratory flow is eliminated altogether. This allows the patient to interact with the training system in a manner essentially equivalent to that which occurs in the normal use of a hand held inhaler. This is possible because whereas the canister holding component of a MDI is designed to allow sufficient airflow during inspiration, it does not provide a channel for unimpeded flow of expiratory air through the inhaler. To measure directional flow during aerosol usage, the Hillsman 1991 system attaches the MDI canister to an airflow channel through which the patient must breathe both in and out. In contrast, using the present invention the patient holds the MDI in hand during inhalation just as in everyday use, and removes the device from his mouth at the end of inhalation as in everyday use. This manner of MDI use is likely to be more effective in training since it more closely recreates the technique and situation of actual MDI use.
Another disadvantage of the Hillsman design is the requirement for the patient to direct his attention to the volume signal and hold the flow tube in his mouth throughout the breath hold stage. This procedure is counter to the normal practice during MDI usage wherein the patient removes the inhaler from his mouth at the completion of inhalation. Patients are in fact specifically instructed in the inhaler medication package insert not to breath out through the inhaler, since this may clog the MDI nozzle with exhaled medicine. In the Hillsman system the volume-time signal is also used as the primary feedback mechanism to the patient regarding the duration of breath holding. The message format utilized in the present invention, a timer, written message, and/or graphic portrayal of dynamic aerosol deposition via sedimentation and diffusion, is again more intuitively understood by the patient and is compatible with the normal circumstance and feel of MDI usage.
An advantage of the present invention is the use of patient feedback display types which are inherently more responsive and interactive than a volume-time graph. By employing a flow-time or flow-volume graph as feedback to the patient, subtle changes in inhalation rate are conveyed almost instantaneously. Moreover, since a primary object of the training is to teach the feeling associated with correct inhalation flow rate, the use of flow as a primary feedback signal is more intuitive to the patient.
In summary, the foregoing conventional inhalation training devices ignore or discount variables which are important in maximizing the amount of and rate at which the aerosol medication is delivered to the receptor sites in the lungs. Conventional devices also ignore the complexity of mechanisms responsible for the deposition patterns of an aerosol medication in the lungs.
Conventional devices do not offer the patient a visual form of feedback from which to conceptualize the process of medication delivery. Typical feedback mechanisms such as red and green lights, analog needle gauges, or alphanumeric characters indicating "good" are merely generalized, gross indications of the amount of air inspired. Effectively, such gross indicators are, in principle, unchanged from devices wherein the feedback consists of an object rising in a calibrated tube. Simple graphs of lung volume are similarly inadequate to convey the needed conceptual understanding.
Thus, there presently exists a need for a device which provides meaningful visual feedback to a patient in order to train the patient to use an aerosol inhaler effectively over the long term.
The typical inhaler devices and training aids have little or no diagnostic value and provide the physician with little or no meaningful objective feedback concerning the capability of a particular patient to effectively utilize aerosol therapy devices. There is also a need for an inhalation training device which can be used simultaneously by the patient and the medical professional and which can present to the medical professional a detailed illustration of the overall pattern of individual patient performance as opposed to a general indication of good or bad performance. There is also a need for visual feedback provided to a patient or healthcare professional that is directly related to and indicative of the complex physiological parameters which are different for each patient and which largely determine the pattern of distribution of the aerosol medication at the receptor sites in the lungs.
In order to improve the aerosol delivery of medication, what is needed is a device which takes into account a maximum number of meaningful parameters affecting aerosol distribution at the receptor sites in the lungs. These parameters include airflow rate, inhalation volume, duration of inhalation, duration of breath holding and patient-specific pulmonary function values such as vital capacity and timed flow rates, and disease conditions such as obstructive illnesses which lower the optimal inhalation rate. What is also needed is a method for interpreting the values of the variables affecting aerosol distribution and utilizing this interpretation to modulate the feedback display to the patient to produce meaningful interactive visual feedback representing the present state of delivery of medication to the target receptor sites in the patients' lungs.
Therefore, what is needed is an apparatus and visual display method which provides meaningful feedback to a patient and healthcare professional in order to train the patient to effectively use an aerosol inhaler over the long term. This system would recreate the normal feeling of hand held inhaler usage, and convey a conceptual understanding of the correct, although counterintuitive, inspiration and breath holding pattern. Such a system would teach the patient the specific skills required to affect delivery of medication to is target sites of action.